Cross-sectoral sharing of CTX-M-producing <i>Escherichia coli</i> : a One Health analysis to understand dissemination modes

CTX-M-producing <i>Escherichia coli</i> represents a significant global source of infections, and mitigating its rising prevalence demands a comprehensive understanding of its reservoirs and cross-sectoral distribution. To investigate this, we conducted a One Health surveillance study in Hong Kong (2018-2023), performing a cross-sectoral genomic comparison of CTX-M-producing <i>E. coli</i>. A total of 3,213 samples were collected, of which 397 tested positive, including ready-to-eat foods (0.6%, 13/2,119), raw meats (30.0%, 232/774), 217 animal feces (66.4%, 144/217), and food-processing surfaces (7.8%, 8/103). Genomic analysis was performed on all isolated CTX-M-producing <i>E. coli</i> strains, which were compared with human clinical isolates. Our results revealed a diverse genomic population of CTX-M-producing <i>E. coli</i>, with most isolates clustering in sector-specific groups, suggesting limited cross-sectoral transmission. In contrast, the <i>bla</i>_CTX-M-14 and <i>bla</i>_CTX-M-55 variants were detected across all sectors exhibiting broader dissemination. Dissemination of <i>bla</i>_CTX-M across these sectors was primarily mediated by transposons (notably Tn<i>Ecp1.1</i> and Tn<i>6339</i>, driven by IS<i>Ecp1</i>), with plasmids playing a secondary role. However, clonal dissemination of <i>bla</i>_CTX-M between human and non-human sectors was rare. These findings delineate the primary mode of <i>bla</i>_CTX-M spread and provide a novel assessment to refine antimicrobial resistance surveillance strategies.IMPORTANCEThe rising prevalence of CTX-M-producing <i>Escherichia coli</i> poses a severe global threat to public health by undermining the effectiveness of essential antibiotics. Our comprehensive One Health study provides a critical breakthrough by identifying the primary mechanism behind the spread of the <i>bla</i>_CTX-M gene. Our research demonstrates that the critical antibiotic resistance gene <i>bla</i>_CTX-M spreads across human, animal, and food origins not primarily through the transmission of the bacteria themselves, but through mobile genetic elements called transposons. This is a pivotal distinction for public health. It means that surveillance efforts must expand beyond tracking bacterial outbreaks to specifically monitor these mobile gene carriers. By identifying transposons as the main drivers of cross-sectoral spread, our work provides a new and more effective target for strategies aimed at containing the global threat of antimicrobial resistance.